Cesium carbonate → N-(1,2-dimethyl-3-(1-methylindolin-6-yl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1-methyl-1H-pyrazole-3-sulfonamide

HRID 331061Notes

Reaction equation

HRID 331061 reaction equation
Br[C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8]([CH3:22])[C:9]([CH3:21])=[C:10]([C:11]3[CH:19]=[C:18]4[C:14]([CH2:15][CH2:16][N:17]4[CH3:20])=[CH:13][CH:12]=3)[C:3]=12.[CH3:23][N:24]1[CH:28]=[CH:27][C:26]([S:29]([NH2:32])(=[O:31])=[O:30])=[N:25]1.C(=O)([O-])[O-].[Cs+].[Cs+].CN(C)C1C=CC=CC=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:22][N:8]1[C:4]2=[N:5][CH:6]=[CH:7][C:2]([NH:32][S:29]([C:26]3[CH:27]=[CH:28][N:24]([CH3:23])[N:25]=3)(=[O:31])=[O:30])=[C:3]2[C:10]([C:11]2[CH:19]=[C:18]3[C:14]([CH2:15][CH2:16][N:17]3[CH3:20])=[CH:13][CH:12]=2)=[C:9]1[CH3:21]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 148356431-methyl-1H-pyrazole-3-sulfonamideHCID 710901424-bromo-1,2-dimethyl-3-(1-methylindolin-6-yl)-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 71090219N-(1,2-dimethyl-3-(1-methylindolin-6-yl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1-methyl-1H-pyrazole-3-sulfonamideYield 24%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of 4-bromo-1,2-dimethyl-3-(1-methylindolin-6-yl)-1H-pyrrolo[2,3-b]pyridine (D28) (85 mg, 0.239 mmol) in 1,4-dioxane (2 mL) was added 1-methyl-1H-pyrazole-3-sulfonamide (D94) (65.4 mg, 0.406 mmol), cesium carbonate (155 mg, 0.477 mmol), Pd2(dba)3 (16.39 mg, 0.018 mmol) and 2-(dimethylamino)-2′-(dicyclohexylphosphino)biphenyl (14.08 mg, 0.036 mmol). The reaction mixture was heated in the microwave at 150° C. for 30 mins. The reaction mixture was filtered through celite washing with ethyl acetate and the resulting solution evaporated to dryness. The residue was purified by column chromatography on silica gel, eluting with a gradient of 0-100% ethyl acetate in cyclohexane to afford a material which was further purified by MDAP (basic condition) to afford the title compound (25 mg). LCMS (A): m/z (M+H)+ 437, C22H24N6O2S requires 436 (acidic).

Workup

  1. filtrationThe reaction mixture was filtered
  2. washthrough celite washing with ethyl acetate
  3. customthe resulting solution evaporated to dryness
  4. customThe residue was purified by column chromatography on silica gel
  5. washeluting with a gradient of 0-100% ethyl acetate in cyclohexane
  6. customto afford a material which
  7. customwas further purified by MDAP (basic condition)

Sources & evidence

ORD record
ord-4023e28a3fd3421bbe35fef28ca53e9b
Source dataset
uspto-grants-2014_11
Patent number
US08877742B2

Reaction notes

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